The present invention relates to nanoparticles comprising a poorly water-soluble drug, a poorly aqueous soluble non-ionizable polymer and an amine-functionalized methacrylate copolymer.
A variety of approaches have been taken to formulate drugs as nanoparticles. One approach is to decrease the size of crystalline drug by grinding or milling the drug in the presence of a surface modifier. See, e.g., U.S. Pat. No. 5,145,684. Another approach to forming nanoparticles is to precipitate the drug in the presence of a film forming material such as a polymer. See, e.g., U.S. Pat. No. 5,118,528.
Amine-functionalized methacrylate copolymers, such as Eudragit RL100® and Eudragit RS100® have been used in nanoparticle compositions. See, for example, Bucolo et al., J. Pharmacy and Pharmacology, 2004, 56, 841-846; Pignatello et al., J. Pharm. Sci., 2002, Vol. 91, No. 12, 2636-2641; and Rabinovich-Guilatt, et al., J. Drug Targeting, 2004, Vol. 12 (9-10), 623-633. Nanoparticles of a polymer and a positively charged polysaccharide have also been made, with a therapeutic substance associated with the nanoparticle. See, for example, US Published Patent Application 2006/0134220.
Alonso Fernandez et al., U.S. Pat. No. 6,649,192 B2 disclose nanoparticles for the administration of macromolecules comprising a combination of hydrophilic polymers. The polymers are chitosan (an aminopolysaccharide) or its derivatives and optionally polyoxyethylene or its derivatives.
Shefer et al., U.S. Pat. No. 6,565,873 B1 disclose nanoparticles having an average particle diameter of from about 20 nm to about 10 microns, which comprise a biodegradable solid hydrophobic core and a bioadhesive/mucoadhesive positively charged surfactant that is entrapped and fixed to the particle surface. The nanoparticles are for delivery to an oral cavity or mucous membranes.
Maincent et al., US Pub. Patent Application 2005/0013866 A1 disclose particulate vectors for increasing the absorption of actives comprising at least one biodegradable polymer combined with at least one polycationic polymer. The particulate vectors may be nanoparticles.
Aboubakar, et al. US Published Patent Application 2006/0134220 disclose nanoparticles of a polymer and a positively charged polysaccharide. The drug is adsorbed to the nanoparticle.